The Gateway Hypothesis of substance abuse: developmental, biological and societal perspectives

Acta Paediatr. 2015 Feb;104(2):130-7. doi: 10.1111/apa.12851. Epub 2014 Dec 2.


The Gateway Hypothesis describes how tobacco or alcohol use precedes marijuana and other illicit drug use. We review the epidemiological data, explore the underlying molecular mechanisms in mice and discuss the societal implications of the hypothesis, including the use of e-cigarettes by young people.

Conclusion: Our mouse model identifies biological processes underlying the hypothesis, showing that nicotine is a gateway drug that exerts a priming effect on cocaine through increased global acetylation in the striatum.

Keywords: Cocaine; E-cigarettes; Gateway Hypothesis; Histone acetylation; Nicotine.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Cocaine / pharmacology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Dopamine Uptake Inhibitors / pharmacology
  • Ganglionic Stimulants / pharmacology
  • Humans
  • Nicotine / pharmacology
  • Substance-Related Disorders / epidemiology
  • Substance-Related Disorders / etiology*
  • Substance-Related Disorders / metabolism
  • Substance-Related Disorders / psychology


  • Dopamine Uptake Inhibitors
  • Ganglionic Stimulants
  • Nicotine
  • Cocaine